The aim of this study was to evaluate the influence of different cavity preparation designs on marginal accuracy of laboratory-processed resin composite restored teeth. Eighty mandibular human third molars were selected. There were two experimental factors, occlusal isthmus width (narrow vs wide) and cuspal coverage (inlay, one-cusp onlay, two-cusp onlay, and all-cusp onlay), resulting on eight groups (N = 10). Indirect composite restorations (SR Adoro, Ivoclar-Vivadent) were manufactured and positioned over each respective preparation. Marginal accuracy evaluation was accomplished using a stereomicroscope at three points on buccal, lingual, mesial, and distal regions with 40x magnification. The results showed significant differences (P = 0.00) with wide inlay showing the best overall marginal accuracy and narrow inlay the worst one. Two-way analysis of variance (ANOVA) showed significant differences when considering the factor occlusal isthmus width (P = 0.00). In general, preparations with wide occlusal isthmus presented better results than narrow ones, except for wide all-cusp onlays; however, the test failed to show differences when considering the cuspal coverage (P = 0.42) or the interaction between both factors (P = 0.30). The effect of occlusal width extension on marginal accuracy of indirect composite resin restorations is significant, with lower values of gaps width in wide preparations, but since in a clinical situation this would mean greater removal of sound tooth structure, less-aggressive preparations combined with other restorative procedures seem to be more feasible.